Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers.
Epidermal growth factor (EGF) is a potent mitogen for human mesothelial cells, and autophosphorylation of the EGF receptor (EGF-R) occurs in these cell types after exposure to asbestos, a carcinogen associated with the development of mesothelioma. Here, the intensity and distribution of EGF-R protein was documented by immunocytochemistry in a human mesothelial cell line (MET5A) exposed to various concentrations of crocidolite asbestos and man-made vitreous fibers (MMVF-10). Whereas cells in contact with or phagocytizing shorter asbestos fibers (<60 microm length) or MMVF-10 at a range of concentrations showed no increase in EGF-R protein as determined by immunofluorescence, elongated cells phagocytizing and surrounding longer fibers (> or =60 microm) showed intense staining for EGF-R. In contrast, human A549 lung carcinoma cells showed neither elongation nor increased accumulation of EGF-R protein in response to long fibers. Patterns of aggregation and increases in EGF-R protein in mesothelial cells phagocytizing long asbestos fibers were distinct from diffuse staining of phosphotyrosine residues observed in asbestos-exposed cultures. These studies indicate that aggregation of EGF-R by long fibers may initiate cell signaling cascades important in asbestos-induced mitogenesis and carcinogenesis.
Pache
J C
JC
Department of Pathology, University of Vermont College of Medicine, Burlington 05405, USA.
Janssen
Y M
YM
Walsh
E S
ES
Quinlan
T R
TR
Zanella
C L
CL
Low
R B
RB
Taatjes
D J
DJ
Mossman
B T
BT
D001194:Asbestos / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D019000:Phosphotyrosine / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002273:Carcinogens; D001194:Asbestos; D019000:Phosphotyrosine; D066246:ErbB Receptors